1. Field of the Invention
The present invention relates to a process for purifying eicosapentaenoic acid and its esters and more particularly to a process for purifying eicosapentaenoic acid and its esters to a high concentration on an industrial scale from natural fats and oils containing eicosapentaenoic acid or its derivatives.
2. Description of the Prior Art
It is known that eicosapentaenoic acid (which may hereinafter be referred to simply as "EPA") and its esters or amides are effective for medically treating or preventing certain thrombotic conditions such as myocardial or cerebral infarction (Japanese Laid-open Patent Application No. 15444/80).
Eicosapentaenoic acid is found in natural fats and oils, particularly in the fats and oils of marine animals such as the mackerel, sardine, or cod, either as itself or in the form of a derivative, such as a glyceride. Unfortunately, other fatty acids are always present in larger amounts. Although EPA is known to have the abovementioned medicinal effectiveness, it is still necessary for extensive basic studies, including clinical studies, to be conducted before EPA can be marketed as a medicine. For such studies, highly pure EPA is required in large amounts. However, prior to the present invention, there was no industrial method which was useful for separating EPA in a high concentration from natural fats and oils. This has been a bottleneck in the development of EPA as a medicine.
In order to concentrate a particular fatty acid from a mixture of various fatty acids or their esters, it has been common to use various methods such as dewaxing, counter current extraction, urea addition, distillation, liquid chromatography, and the like, depending upon the particular composition of the mixture of fatty acids available as the raw material. These methods have been used chiefly for the separation of relatively low molecular weight fatty acids from other fatty acids, or for the separation of saturated acids from unsaturated acids. The present situation is different from these previous separations. EPA is a highly unsaturated fatty acid having 20 carbon atoms and 5 double bonds. As is evident from its structure, it is quite unstable when exposed to oxygen, light, or heat. In fact, only with recent developments in the field of gas chromatography has the quantitative analysis of EPA become possible. Accordingly, it is difficult to readily and economically concentrate and separate EPA using the above-mentioned conventional methods.
Among the above-mentioned conventional methods, for instance, counter current extraction and liquid chromatography methods have been shown to be useful for the separation of EPA on a small scale. However, such methods require large amounts of various solvents and a long period of time. Accordingly, from the economic and practical points of view, they are totally unsatisfactory in industrial situations.